Conclusion: Post-op RT better for LRC (especially in SGL), but no impact on OS due to distant failure and second primaries

Comment: some argument for definitive chemoRT instead of surgery and post-op RT since after 2 yrs, distant mets are primary cause of failure resulting in similar 10 OS in this trial. LRC still better for post-op vs definitive RT alone. Also, different doses used, at the time believed equivalent given the setting

Randomized. 424 pts. Stage III-IV, scca of oropharynx, hypopharynx, or layrnx. 56-63% had tumors of the oropharynx. Randomized to RT +/- cetuximab. Given as 400 mg/m2 loading dose IV one week before RT, followed by weekly infusions of 250 mg/m2 during RT.

EditorialPMID 16467552: RT alone in the control arm is suboptimal therapy; current standard of care is RT + cisplatin, which has shown greater benefit than cetuximab. Also, cetuximab appeared only effective in the hyperfractionated arms. No survival benefit for hypopharynx and larynx subgroups. Standard of care should still be RT + cisplatin, but if not tolerated, then cetuximab a good option

1989PMID 2689395 -- "The role of hemoglobin concentration in the outcome of misonidazole-sensitized radiotherapy of head and neck cancers: based on RTOG trial #79-15." (Fazekas JT, Int J Radiat Oncol Biol Phys. 1989 Dec;17(6):1177-81.)

Outcome: second primary tumors isotretinoin 14% vs. placebo 31% (SS); but impact diminishes with time. By 8 years, estimated rates of 19% vs. 44%. No patients developed second primary tumor while on drug

Comment: First randomized trial to show a survival benefit for the use of concurrent chemo, unexpectedly low RT alone outcome (several retrospective series showed >70% OS with RT alone in endemic patients), RT technique considered less aggressive than that practiced in Asia (particularly lack of parapharyngeal and intracavitary boost), not applicable to non-US patients

Randomized, 3 arms. 518/547 patients. Stage III or IV cancers of the glottic or supraglottic larynx, which would require total laryngectomy. Excluded T1 and large volume T4 (penetrating through cartilage or >1cm into BOT). Arm 1) Induction cisplatin 100 mg/m2 + 5-FU C.I. 1000 mg/m2 Q3W x3 cycles, followed by RT (if CR or PR) or laryngectomy if poor response (this Arm based on results of the VA Larynx trial) vs. Arm 2) Concurrent cisplatin 100 mg/m2 Q3W + RT vs. Arm 3) RT alone. RT dose was 70/35, elective neck and SCV 50/25. Patient in the first arm who had salvage surgery for poor response to chemo received adjuvant RT to 50-70 Gy depending on surgical margin status. Planned lymph node dissection was performed for LN > 3cm or multiple lymph nodes at original staging. In induction group, 83% continued to RT and most of others received more chemotherapy or RT but not surgery. End point was preservation of larynx

Larynx preservation: induction 72% (SS) vs. concurrent 84% vs. RT alone 67% (SS). No benefit to induction chemo over RT alone. Laryngectomy-free survival at 2-years and 5-years was 59%/43% (induction), 66%/45% (concurrent), and 53%/38% (RT alone), with no S.S. difference between the two chemo groups but a S.S. difference between concurrent and RT alone. There was no difference in LFS between the two chemo arms due to an increase in intercurrent deaths for the concomitant group.

Larynx preservation in 64%. Half of laryngectomies were before RT (poor response to chemo) and the other half were after RT, with most of these from persistent tumor and only 7% from recurrence.

Survival 68% vs 68% at 2 years. No difference in survival for the pts who responded to chemo vs those who did not. No S.S. difference in DFS between chemo/RT and surgery groups. Overall recurrence rate not S.S. different between 2 groups but pattern of recurrence differed, with more recurrence at the primary site (12% vs 2%) in chemo/RT group vs more distant mets in surgery group (17% vs 11%).

Editorial (PMID 19176460): larynx preservation defined as survival with larynx without tumor, tracheotomy or use of feeding tube, which gives these states equal utility as death; other issues with endpoints used for larynx preservation. Need a common standardized endpoint

Outcome: Mucositis days Caphosol 3.7 days vs. control 7.2 days (SS); duration of pain 2.9 vs. 7.7 (SS); morphine dose 34 mg vs. 123 mg, days of morphine 1.3 days vs. 4.0 days (SS); and days to onset of ANC 11.1 days vs. 12.6 days

Toxicity: No difference in G3 dysphagia. PEG site infections 27%, NGT dislodgement 61%. No difference in chest infection. QoL overall no difference, but more pain with PEG (SS), more inconvenience with NGT (SS), more altered body image with NGT (SS) during first week. No difference at removal.